4mo2 | pdb_00004mo2

Crystal Structure of UDP-N-acetylgalactopyranose mutase from Campylobacter jejuni

spinqualitylabelsall models 4mo2, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4mo2 is a 2 chain structure with sequence from Camje. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FAD, FDA, GOL, NH4, SO4 Gene: Cj1439c, glf (CAMJE) Activity: UDP-galactopyranose mutase, with EC number 5.4.99.9 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Pyranose-furanose mutases are essential enzymes in the life cycle of a number of microorganisms, but are absent in mammalian systems, and hence represent novel targets for drug development. To date, all such mutases show preferential recognition of a single substrate (e.g., UDP-Gal). We report here the detailed structural characterization of the first bifunctional pyranose-furanose mutase, which recognizes both UDP-Gal and UDP-GalNAc. The enzyme under investigation (cjUNGM) is involved in the biosynthesis of capsular polysaccharides (CPSs) in Campylobacter jejuni 11168. These CPSs are known virulence factors that are required for adhesion and invasion of human epithelial cells. Using a combination of UV/visible spectroscopy, X-ray crystallography, saturation transfer difference NMR spectroscopy, molecular dynamics and CORCEMA-ST calculations, we have characterized the binding of the enzyme to both UDP-Galp and UDP-GalpNAc, and compared these interactions with those of a homologous monofunctional mutase enzyme from E. coli (ecUGM). These studies reveal that two arginines in cjUNGM, Arg59 and Arg168, play critical roles in the catalytic mechanism of the enzyme and in controlling its specificity to ultimately lead to a GalfNAc-containing CPS. In ecUGM, these arginines are replaced with histidine and lysine, respectively, and this results in an enzyme that is selective for UDP-Gal. We propose that these changes in amino acids allow C. jejuni 11168 to produce suitable quantities of the sugar nucleotide substrate required for the assembly of a CPS containing GalfNAc, which is essential for viability. Specificity of a UDP-GalNAc Pyranose-Furanose Mutase: A Potential Therapeutic Target for Campylobacter jejuni Infections.,Poulin MB, Shi Y, Protsko C, Dalrymple SA, Sanders DA, Pinto BM, Lowary TL Chembiochem. 2014 Jan 3;15(1):47-56. doi: 10.1002/cbic.201300653. Epub 2013 Dec, 2. PMID:24302429 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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